Alternative titles; symbols
HGNC Approved Gene Symbol: KIFC1
Cytogenetic location: 6p21.32 Genomic coordinates (GRCh38) : 6:33,391,461-33,409,896 (from NCBI)
Janatipour et al. (1992) identified the HSET gene within a segment centromeric to the class II gene region of the human major histocompatibility complex. By screening a human testis library with a cDNA corresponding to Tctex7, the mouse homolog of HSET, Ando et al. (1994) isolated human HSET cDNAs. Northern blot analysis revealed that the 2.4-kb HSET mRNA is expressed in several human cell lines. The C-terminal 350 amino acids of the predicted HSET protein share extensive homology with the ATP-binding and motor domains of kinesin heavy chain (148760) and the kinesin-related proteins CENPE (117143) and MKLP1. Although the mechanochemical domain of kinesin and kinesin-like proteins is generally located within the N-terminal region, HSET contains a C-terminal mechanochemical domain. This 'reversed' structural organization is also found in the S. cerevisiae KAR3 and Drosophila Ncd kinesin-like proteins.
Molecular motors move directionally to either the plus or the minus ends of microtubules or actin filaments. For example, kinesin (see 600025) moves towards the plus end, whereas the Drosophila Ncd motor moves towards the minus end. Endow and Higuchi (2000) showed that an asn340-to-lys mutation in the 'neck' (the region between the stalk and the C-terminal motor domain) of Ncd, which corresponds to a KAR3 mutation obtained in a yeast suppressor screen (Hoyt et al., 1993), causes the motor to abruptly reverse directions and move toward either the plus or minus end. Velocity in mutant and wildtype was identical, indicating that the neck was functional. Mutation of lys640, which is located in the motor-core region and touches asn340 in crystal structures, to asn caused the same phenotype. Analysis of a double mutant for these residues, which did not revert to minus-end directionality, indicated that the highly conserved residues do not interact normally in an inverted configuration. Endow and Higuchi (2000) concluded that directional bias is dependent on neck/motor-core interactions.
Janitz et al. (1999) reported the genomic structure of the complete HSET gene together with its flanking loci. Sequence analysis of the 40-kb cosmid clone containing the HSET gene revealed the presence of several new genes not related to the kinesin superfamily.
By inclusion within mapped clones, Ando et al. (1994) mapped the HSET gene to within 220 kb of the HKE4 (601416) gene, which is located at 6p21.3.
Lawrence et al. (2004) presented a standardized kinesin nomenclature based on 14 family designations. Under this system, KIFC1 belongs to the kinesin-14 family.
Janitz et al. (1999) studied the possible involvement of the HSET gene and the beta-tubulin gene (TUBB; 191130) in the pathogenesis of immotile cilia syndrome (see 244400) by screening 2 unrelated ICS families with microtubule defects and suspected HLA linkage for mutations within the HSET and TUBB genes. Four single-base substitutions were identified in the HSET gene, and none were identified in the TUBB gene. On the basis of these data, the authors considered a role of the HSET and TUBB gene products in the pathogenesis of ICS in the 2 families unlikely.
Ando, A., Kikuti, Y. Y., Kawata, H., Okamoto, N., Imai, T., Eki, T., Yokoyama, K., Soeda, E., Ikemura, T., Abe, K., Inoko, H. Cloning of a new kinesin-related gene located at the centromeric end of the human MHC region. Immunogenetics 39: 194-200, 1994. [PubMed: 8276466] [Full Text: https://doi.org/10.1007/BF00241260]
Endow, S. A., Higuchi, H. A mutant of the motor protein kinesin that moves in both directions on microtubules. Nature 406: 913-916, 2000. [PubMed: 10972296] [Full Text: https://doi.org/10.1038/35022617]
Hoyt, M. A., He, L., Totis, L., Saunders, W. S. Loss of function of Saccharomyces cerevisiae kinesin-related CIN8 and KIP1 is suppressed by KAR3 motor domain mutations. Genetics 135: 35-44, 1993. [PubMed: 8224825] [Full Text: https://doi.org/10.1093/genetics/135.1.35]
Janatipour, M., Naumov, Y., Ando, A., Sugimura, K., Okamoto, N., Tsuji, K., Abe, K., Inoko, H. Search for MHC-associated genes in human: five new genes centromeric to HLA-DP with yet unknown functions. Immunogenetics 35: 272-278, 1992. [PubMed: 1541487] [Full Text: https://doi.org/10.1007/BF00166833]
Janitz, K., Wild, A., Beck, S., Savasta, S., Beluffi, G., Ziegler, A., Volz, A. Genomic organization of the HSET locus and the possible association of HLA-linked genes with immotile cilia syndrome (ICS). Immunogenetics 49: 644-652, 1999. [PubMed: 10369922] [Full Text: https://doi.org/10.1007/s002510050660]
Lawrence, C. J., Dawe, R. K., Christie, K. R., Cleveland, D. W., Dawson, S. C., Endow, S. A., Goldstein, L. S. B., Goodson, H. V., Hirokawa, N., Howard, J., Malmberg, R. L., McIntosh, J. R., and 10 others. A standardized kinesin nomenclature. J. Cell Biol. 167: 19-22, 2004. [PubMed: 15479732] [Full Text: https://doi.org/10.1083/jcb.200408113]